Childhood Cancer Survivors' Reported Late Effects, Motivations for Seeking Survivorship Care, and Patterns of Attendance.

BACKGROUND: Childhood cancer survivors are vulnerable to long-term treatment-related health conditions, which can lead to poor quality of life. Little data exist on the overall health of long-term Australian and New Zealand childhood cancer survivors or on survivors' motivations for attending survivorship clinics. METHODS: This study administers a cross-sectional questionnaire to long-term survivors ≥5 years from their primary diagnosis. We compared participant-reported number of late effects by a cancer diagnosis, and identified clinical (eg, treatment) and demographic (eg, age) factors that were associated with late effects burden and engagement in cancer survivorship care. RESULTS: A total of 634 participants completed questionnaires (48% male, mean age = 21.7 years). Most participants (79%) reported at least one cancer-related late effect, most commonly fatigue (40%) and memory/learning difficulties (34%). Brain tumor survivors reported a higher total number of late effects than survivors with other diagnoses (mean = 5.7 vs. 3.2, P < .001). Participants' most commonly reported motivators for engaging in care were to understand problems that may occur later in life because of their cancer and/or treatment (98.5%) and to get reassurance about one's health (97.4%). The proportion of survivors endorsing each motivating factor was similar across cancer diagnoses, with the exception of learning more about insurance and pensions (highest in brain tumor survivors = 80%). In multivariable analyses, survivors were more likely to report being engaged in survivorship care if they were younger (P < .001), less time had elapsed since their diagnosis (P < .001), or they reported a higher number of motivating factors (P = .016). CONCLUSION: Survivors report a range of health problems decades after treatment completion. Understanding the burden of late effects, and motivators for seeking survivorship care to manage these health problems, is important for ensuring that tailored interventions or services are available to meet the needs of this growing population and to design effective models of survivorship care.

Sexual and reproductive complications and concerns of survivors of childhood, adolescent and adult cancer.

PURPOSE: Cancer survivors may experience infertility and sexual dysfunction following cancer treatment. Survivors report significant gaps in oncofertility care and consider these issues important, yet they are rarely discussed. The aims of this study were to evaluate survivors' sexual and reproductive complications across age groups and to identify specific groups of survivors at risk for sexual and reproductive complications. METHOD: We report data collected from survivors of cancers diagnosed in childhood, adolescence and adulthood following the development and piloting of a reproductive survivorship patient reported outcome measure (RS-PROM). RESULTS: One hundred and fifty survivors participated in the study (mean age at cancer diagnosis was 23.2 years [SD, 10.3 years]). About 68% of participants expressed concerns about their sexual health and function. Survivors (50%) expressed at least one body image concern, with the female gender the most common risk factor for all subgroups. A total of 36% of participants reported at least one concern regarding their fertility, with more male than female survivors reporting fertility preservation prior to treatment. Females compared with male participants were more likely to feel less physically attractive after treatment (OR = 3.83, 95% CI = 1.84-7.95, p < 0.001). More females than males were also more likely to feel dissatisfied with the appearance of a scar(s) after treatment (OR = 2.36, 95% CI = 1.13-4.91, p = 0.02). CONCLUSION: The RS-PROM identified multiple reproductive complications and concerns for cancer survivors in the survivorship period. IMPLICATIONS FOR CANCER SURVIVORS: Utilising the RS-PROM in conjunction with a clinic appointment could help identify and address cancer patients' concerns and symptoms.

Evaluating the quality and safety of the BreastScreen remote radiology assessment model of service delivery in Australia.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer in Australian women. Given the diverse geography and populations within Australia, the ability to offer a telemedicine-supported breast screening and assessment service may increase access. The aim of this study was to assess clinical outcomes of a telemedicine-based remote radiology assessment service delivery model for detecting breast cancer in regional Australian women compared to the traditional radiologist onsite model. METHODS: This study was a pre-post intervention study using de-identified administrative data. Data were collected from seven sites across three health jurisdictions within Australia. There were a total of 21,117 assessment visits, with 10,508 (49.8%) pre- and 10,609 (50.2%) post-remote model implementation. Of the 10,609 post-remote model visits, 3,904 (36.8%) were under the remote model. The main outcome was cancer detection, split into any cancer, any invasive cancer or any small invasive cancer. Timeliness of assessment was also examined. RESULTS: After adjusting for multiple factors, there were no statistically significant differences in cancer detection rates between the remote and onsite models (adjusted odds ratio (AOR) = 1.02, 95% CI 0.86-1.19, n.s.). Implementing the remote assessment model had statistically significant positive effects on the timeliness of assessment (AOR = 0.68, 95% CI 0.59-0.77, p < 0.001). DISCUSSION: This study found the remote model delivers safe and high-quality assessment services, with equivalent rates of cancer detection and improved timeliness of assessment when compared to the traditional onsite model. Careful monitoring and ongoing evaluation of any health-service model is important for ongoing safety, efficiency and acceptability.

Childhood cancer survivorship care: A qualitative study of healthcare providers' professional preferences.

Purpose: Childhood cancer survivorship care is a complex specialty, though it is increasingly being integrated into the general practitioner's (GP) remit. Establishing the essential components of tertiary- and primary-led care, to maximize the benefits and overcome the challenges inherent to each, is essential to inform the development of survivor-centered, sustainable care models. Methods: We used the qualitative principles of semi-structured interviewing, verbatim transcription, coding (supported by NVivo12) and thematic analysis, to collect and evaluate the views and preferences of pediatric oncologists, survivorship nurse coordinators, and GPs currently caring for childhood cancer survivors. Results: Seventy healthcare providers (19 oncology staff and 51 GPs) from 11 tertiary hospitals and 51 primary practices across Australia and New Zealand participated. Participants reported specialist expertise and holistic family-centered care as the key benefits of tertiary and primary care respectively. Participants reported that tertiary-led survivorship care was significantly challenged by a lack of dedicated funding and costs/travel burden incurred by the survivor, whereas primary-led survivorship care was challenged by insufficient GP training and GPs' reliance on oncologist-developed action plans to deliver guideline-based care. GPs also reported a need for ongoing access to survivorship expertise/consultants to support care decisions at critical times. The discharge of survivors into primary care limited late-effects data collection and the rapid implementation of novel research findings. Conclusions: Healthcare professionals report that while a risk-stratified, collaborative model of survivor-centered care is optimal, to be implemented successfully, greater provisions for the ongoing engagement of GPs and further access to GP education/training are needed.

Childhood Cancer Survivors' Adherence to Healthcare Recommendations Made Through a Distance-Delivered Survivorship Program.

Purpose: Ongoing survivorship care allows childhood cancer survivors the opportunity to address treatment-related health problems and improve their quality of life. However, many survivors do not adhere to their healthcare professionals' recommendations and the factors supporting their adherence remain unclear. Patients and Methods: Long-term childhood cancer survivors completed the "Re-engage" program, which assessed survivors' heath needs and provided individualised recommendations for health interventions and surveillance developed by an expert multi-disciplinary team (MDT). We measured survivors' recall of, and adherence to, their individualised healthcare recommendations at one and six months post-intervention. We conducted a series of univariate negative binomial regressions to investigate factors associated with the total number of recommendations that were correctly recalled and adhered to. Results: We analysed the data of 25 childhood cancer survivors who participated in Re-engage (mean age = 31.9 years). On average, survivors were provided with 6.6 recommendations (range = 1-11). Survivors accurately recalled receiving 3.0 recommendations at one month post-intervention and 1.9 at six months. Survivors had adhered to an average of 1.3 recommendations by six-month follow-up. In total, 56% of participants reported that they did not adhere to any recommendations. By six-month follow-up, greater adherence to MDT recommendations was associated with having a history of a second cancer (B = 1.391; 95% confidence interval [CI], 0.686 to 2.097; p < 0.001) and reporting a greater level of worry about late effects (B = 1.381; 95% CI, 0.494 to 2.269; p = 0.002). Conclusion: Survivors reported sub-optimal levels of adherence and demonstrated limited recall of their healthcare recommendations. Effective communication of recommendations and clear discussion of barriers limiting adherence, coupled with late effects education, may be critical to ensure that survivors engage with their recommendations, to improve their quality of life and health outcomes. Trial Registration Number: ACTRN12618000194268.

eHealth tools for childhood cancer survivorship care: A qualitative analysis of survivors', parents', and general practitioners' views.

Objective: We assessed the acceptability of, and perceived benefits/barriers to, using Electronic health (eHealth) technology for childhood cancer survivorship care. Methods: We interviewed survivors, their parents, and their nominated GP. We described a hypothetical eHealth tool to manage survivorship care and asked their likely use of, and perceived benefits/concerns for, the use of the tool. Results: 31 survivors (mean age = 27.0), 29 parents (survivors' mean age = 12.6), and 51 GPs (mean years practising = 28.2) participated. Most survivors/parents (85%) and GPs (75%) indicated that they would be willing to use an eHealth tool. Survivors/parents reported that an eHealth tool would increase their confidence in their ability, and their GP's ability, to manage their survivorship care. GPs agreed that an eHealth tool would provide easier access to survivors' medical information and increase their capacity to provide support during survivorship. Some GPs (7%) and survivors (43%) reported being hesitant to use eHealth tools due to privacy/security concerns. Conclusion: Overall, eHealth tools appear acceptable and may help to improve the management of late effects for childhood cancer survivors and assist their GPs to coordinate their care. Innovation: Concerns raised by key stakeholders should be addressed in the design of eHealth technologies to optimise their uptake and effectiveness.

Self-Reported Race as a Social Determinant of Stroke Risk in Observational Versus Clinical Trial Datasets.

OBJECTIVES: Self-reported Black (SRB) Americans are approximately twice as likely to have a stroke as self-reported White (SRW) Americans. While social determinants of health and vascular risk factors account for some of the disparity, half the increased risk remains unexplained and may be related to unmeasured real-world factors of the racialized experience. MATERIALS: and Methods In this cohort study, we compared SRB and SRW participants in the Systolic Blood Pressure Intervention Trial (SPRINT) to the same groups in the observational Atherosclerosis Risk in Communities (ARIC) study to evaluate if clinical trial participation mitigates disparities in stroke risk. We set the ARIC baseline at visit 4 and excluded participants with prior stroke to create an ARIC cohort similar in age to SPRINT participants. The study outcome was incident primary stroke. We report hazard ratios from Cox models and inverse-probability weighted Cox models with propensity score matching on participant age, sex, diabetes, atrial fibrillation, and smoking. RESULTS: We included 10,094 patients from ARIC and 8,869 from SPRINT, of which 26.1% were SRB. The risk of stroke between SRW participants in SPRINT versus ARIC was not significantly different (IPW-Weighted HR 0.78 [0.52-1.19]). SRB ARIC participants were twice as likely to have a stroke as SRW ARIC participants (IPW-Weighted HR = 1.96 [1.41-2.71]). However, SRB SPRINT participants did not have higher stroke risk compared to SRW SPRINT or ARIC participants (IPW-Weighted HR 0.99 [0.68--1.77] and 0.95 [.57-1.59], respectively). SRB SPRINT participants in the intensive BP control group had a lower risk of stroke compared to SRB ARIC participants (IPW-Weighted HR = 0.39 [0.20-0.75]). CONCLUSIONS: SRB race, compared to SRW race, is associated with an increase in primary stroke risk in the ARIC study but not in the SPRINT trial. The absence of the racial disparity in stroke incidence in SPRINT indicates that aspects of the disparity are modifiable. Population-based interventions that test this hypothesis deserve further attention.

The lived experience of children and adolescents with cancer.

BACKGROUND: The lived experience of children and adolescents diagnosed with cancer differs greatly from that of the adult cancer patient. A diagnosis of cancer disrupts almost every developmental life stage and continues to affect the child, and potentially their whole family, throughout adulthood. OBJECTIVE: While it is important to recognise the potential for post-traumatic growth, a considerable proportion of children and adolescents will experience poorer psychological, social, educational and quality-of-life outcomes. Parents, particularly mothers, have been shown to experience levels of post-traumatic distress even greater than that of survivors. As such, there exists a critical need to provide family-centred support from diagnosis through to long-term survivorship or bereavement. DISCUSSION: Ongoing surveillance, proactive management of chronic health conditions, and health behaviour education are critical to survivors' lifelong wellbeing and can be facilitated locally by general practitioners with support from tertiary healthcare teams in a shared-care arrangement.

Feasibility, acceptability and appropriateness of a reproductive patient reported outcome measure for cancer survivors.

BACKGROUND: Cancer patients can experience a number of reproductive complications as a result of cancer treatment and may benefit from reproductive preventative health strategies. A Reproductive Survivorship Patient Reported Outcome Measure (RS-PROM) is not currently available but could assist patients address reproductive concerns. PURPOSE: To develop and test the acceptability, feasibility and appropriateness of a RS-PROM tool to be used to assess reproductive needs of cancer survivors aged 18-45 years. METHODS: We reviewed the outcomes of a recently published audit of reproductive care provided in our cancer survivorship clinic to identify gaps in current service provided and used this along with available validated reproductive measures, to develop this pilot RS-PROM. Survivors aged 18-45 years either attending the SCH survivorship clinic over a 1-year period or participants on the Australasian Oncofertility Registry (AOFR) who had agreed to be contacted for future research studies were asked to complete the RS-PROM and a questionnaire on the acceptability, feasibility and appropriateness of content included. RESULTS: One-hundred and fifty patients participated (61.3% females). Median age at cancer diagnosis was 24.5 years (range: 2-45 years). Eighty percent of participants reported the length of the RS-PROM was "just right", 92% agreed they would not mind completing the RS-PROM and 92.7% were willing to answer all questions, with 97% agreeing that the RS-PROM would be an important tool in addressing difficult sexual/reproductive topics concerning with healthcare professionals. CONCLUSION: The large majority of survivors participating in our pilot study found the RS-PROM to be an acceptable, feasible and useful tool to assist discussions of their sexual and reproductive health concerns and experiences with their clinical team.

Client perceptions of the BreastScreen Australia remote radiology assessment model.

BACKGROUND: Telehealth and teleradiology are increasingly used around the world to facilitate health care provision when the health care provider and clients are separated by distance. The BreastScreen Australia Remote Radiology Assessment Model (RRAM) is an initiative developed to address the challenges of inadequate access to a local radiological workforce in regional Australia. With the growth in telehealth innovations more broadly, the RRAM represents a departure from the traditional onsite model where a radiologist would be co-located with practice staff during assessment clinics. Understanding client satisfaction is an important consideration with new models. This article explores client perceptions of the RRAM including awareness, satisfaction with experiences, confidence in the quality of care being received, and preferences regarding models of service delivery. METHODS: Clients in four BreastScreen services across three Australian states and territories were invited to provide feedback on their experiences of the RRAM. Brief face-to-face interviews based on a survey were conducted at the conclusion of assessment clinic visits. Clients also provided feedback through surveys completed and returned by post, and online. RESULTS: 144 clients completed the survey regarding their experiences of the RRAM. The majority were aged between 50 and 59 years (55/144, 38.2%). Most had attended a BreastScreen service for either screening or assessment on a total of two to five occasions (85/142, 59.9%) in the past. Nearly all women who attended a RRAM clinic expressed satisfaction with their experience (142/143, 99.3%). Clients were aware that the radiologist was working from another location (131/143, 91.6%) and the majority believed there wouldn't be any difference in the care they received between the RRAM and the onsite model (120/142, 84.5%). Clients generally had no particular preference for either the onsite or RRAM model of service delivery. CONCLUSIONS: Clients' high satisfaction with their clinic experiences, high confidence in care being received, and the majority having no preference for either the onsite or remote model indicates their acceptance of the RRAM. Client acceptance of the model supports continuation of the RRAM at these sites and expansion. Findings may inform future telehealth innovations where key health care team members are working remotely.

Reproductive Care of Childhood and Adolescent Cancer Survivors: A 12-Year Evaluation.

Background: Reproductive complications for cancer survivors are identified as one of the top unmet needs in the survivorship period. However, current models of cancer care do not routinely incorporate reproductive follow-up for pediatric or adolescent cancer patients. The Kids Cancer Centre has had a one-stop survivorship clinic that includes the attendance of a gynecologist and fertility specialist for the last 12 years. Methodology: To inform the future development of our reproductive survivorship care, we reviewed the reproductive care our survivorship clinic has provided over a 12-year period, specifically reviewing the electronic and patient records to collect information on the demographics of the patients who used the service and their gonadotoxic risk and associated fertility treatment, their documented reproductive needs and concerns, and information provided on preventative reproductive advice and screening. Main Results: Two hundred seventy-eight patients were seen (397 consultations) for advice and management of reproductive issues, including 189 female patients (68.0%). Survivors' median age at follow-up was 25.0 years (range = 6-50), on average 19.2 years from their primary diagnosis (range = 3-46). The reviewed data had five overarching themes (fertility care, hormone dysfunction, sexual dysfunction, fertility-related psychological distress due to reproductive concerns, and preventative health care), although each theme had a number of components. Patients had on average 2.5 reproductive concerns documented per consultation (range 1-5). The three most commonly documented symptoms or concerns at the initial consultation related to fertility status (43.9%), endocrine dysfunction (35.3%), and contraception advice (32.4%). In patients younger than 25 years, documented discussions were predominately about endocrine dysfunction, fertility status, and contraception, while dominant themes for 26-35-year olds were fertility status, reproductive-related health prevention strategies, contraception, and endocrine dysfunction. Survivors 36-45 years of age prioritized fertility status, pregnancy, and contraception. Fertility preservation (FP) (p = 0.05), preventative health strategies (p = 0.001), and contraception advice (p < 0.001) were more commonly discussed by females than males. Conclusion: Young cancer survivors have multiple ongoing reproductive concerns that change over time. Assessing survivors' reproductive potential following cancer treatment is important as it gives patients who have not completed their family planning an opportunity to explore a possible window to FP or Assisted Reproductive Treatment. Our data can assist in informing the model of care for a reproductive survivorship clinic.

"From the technology came the idea": safe implementation and operation of a high quality teleradiology model increasing access to timely breast cancer assessment services for women in rural Australia.

Breast cancer is the most commonly diagnosed cancer in Australian women. Providing timely diagnostic assessment services for screen-detected abnormalities is a core quality indicator of the population-based screening program provided by BreastScreen Australia. However, a shortage of local and locum radiologists with availability and appropriate experience in breast work to attend onsite assessment clinics, limits capacity of services to offer assessment appointments to women in some regional centres. In response to identified need, local service staff developed the remote radiology assessment model for service delivery. This study investigated important factors for establishing the model, the challenges and enablers of successful implementation and operation of the model, and factors important in the provision of a model considered safe and acceptable by service providers. METHODS: Semi-structured interviews were conducted with service providers at four assessment services, across three jurisdictions in Australia. Service providers involved in implementation and operation of the model at the service and jurisdictional level were invited to participate. A social constructivist approach informed the analysis. Deductive analysis was initially undertaken, using the interview questions as a classifying framework. Subsequently, inductive thematic analysis was employed by the research team. Together, the coding team aggregated the codes into overarching themes. RESULTS: 55 service providers participated in interviews. Consistently reported enablers for the safe implementation and operation of a remote radiology assessment clinic included: clinical governance support; ability to adapt; strong teamwork, trust and communication; and, adequate technical support and equipment. Challenges mostly related to technology and internet (speed/bandwidth), and maintenance of relationships within the group. CONCLUSIONS: Understanding the key factors for supporting innovation, and implementing new and safe models of service delivery that incorporate telemedicine, will become increasingly important as technology evolves and becomes more accessible. It is possible to take proposed telemedicine solutions initiated by frontline workers and operationalise them safely and successfully: (i) through strong collaborative relationships that are inclusive of key experts; (ii) with clear guidance from overarching bodies with some flexibility for adapting to local contexts; (iii) through establishment of robust teamwork, trust and communication; and, (iv) with appropriate equipment and technical support.

Re-Engage: A Novel Nurse-Led Program for Survivors of Childhood Cancer Who Are Disengaged From Cancer-Related Care.

BACKGROUND: Survivors of childhood cancer often experience treatment-related chronic health conditions. Survivorship care improves survivors' physical and mental health, yet many are disengaged from care. Innovative models of care are necessary to overcome patient-reported barriers to accessing survivorship care and to maximize survivors' health. METHODS: We piloted a novel survivorship program, called "Re-engage," a distance-delivered, nurse-led intervention aiming to engage, educate, and empower survivors not receiving any cancer-related care. Re-engage involves a nurse-led consultation delivered via telephone/online to establish survivors' medical history and needs. Participants completed questionnaires at baseline, 1 month postintervention, and 6-month follow-up. RESULTS: A total of 27 survivors who had not accessed survivorship care in the last 2 years participated (median age, 31 years; interquartile range [IQR], 27-39 years); of which, 82% were at high-risk for treatment-related complications. Participation in Re-engage was high (75%) and there was no attrition once survivors enrolled. At 1 month postintervention, 92% of survivors reported that Re-engage was "beneficial," which all survivors reported at 6-month follow-up. Survivors' overall satisfaction with their care increased from 52% before Re-engage to 84% at 1 month postintervention. Survivors' mean self-efficacy scores remained similar from baseline to 1 month postintervention (b = -0.33, 95% CI, -1.31 to 0.65), but increased significantly from baseline to 6-month follow-up (b = 1.64, 95% CI, 0.28-3.00). At 6-month follow-up, 73% of survivors showed an increase in health-related self-efficacy compared with baseline. CONCLUSIONS: Re-engage is a highly acceptable and feasible intervention and promotes health-related self-efficacy, which is integral to survivors being advocates for their own health. Further empirical work is needed to evaluate the long-term efficacy of Re-engage. TRIAL REGISTRATION: ACTRN12618000194268.

Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium.

Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems-such as speech and language, social-emotional development, and learning difficulties-for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors.

The Role of Primary Care Physicians in Childhood Cancer Survivorship Care: Multiperspective Interviews.

BACKGROUND: Primary care physicians (PCPs) are well placed to provide holistic care to survivors of childhood cancer and may relieve growing pressures on specialist-led follow-up. We evaluated PCPs' role and confidence in providing follow-up care to survivors of childhood cancer. SUBJECTS, MATERIALS, AND METHODS: In Stage 1, survivors and parents (of young survivors) from 11 Australian and New Zealand hospitals completed interviews about their PCPs' role in their follow-up. Participants nominated their PCP for an interview for Stage 2. In Stage 2, PCPs completed interviews about their confidence and preparedness in delivering childhood cancer survivorship care. RESULTS: Stage 1: One hundred twenty survivors (36% male, mean age: 25.6 years) and parents of young survivors (58% male survivors, survivors' mean age: 12.7 years) completed interviews. Few survivors (23%) and parents (10%) visited their PCP for cancer-related care and reported similar reasons for not seeking PCP-led follow-up including low confidence in PCPs (48%), low perceived PCP cancer knowledge (38%), and difficulty finding good/regular PCPs (31%). Participants indicated feeling "disconnected" from their PCP during their cancer treatment phase. Stage 2: Fifty-one PCPs (57% male, mean years practicing: 28.3) completed interviews. Fifty percent of PCPs reported feeling confident providing care to childhood cancer survivors. PCPs had high unmet information needs relating to survivors' late effects risks (94%) and preferred a highly prescriptive approach to improve their confidence delivering survivorship care. CONCLUSION: Improved communication and greater PCP involvement during treatment/early survivorship may help overcome survivors' and parents' low confidence in PCPs. PCPs are willing but require clear guidance from tertiary providers. IMPLICATIONS FOR PRACTICE: Childhood cancer survivors and their parents have low confidence in primary care physicians' ability to manage their survivorship care. Encouraging engagement in primary care is important to promote holistic follow-up care, continuity of care, and long-term surveillance. Survivors'/parents' confidence in physicians may be improved by better involving primary care physicians throughout treatment and early survivorship, and by introducing the concept of eventual transition to adult and primary services. Although physicians are willing to deliver childhood cancer survivorship care, their confidence in doing so may be improved through better communication with tertiary services and more appropriate training.

T cell epigenetic remodeling and accelerated epigenetic aging are linked to long-term immune alterations in childhood cancer survivors.

BACKGROUND: Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory diseases in cancer survivors. RESULTS: To test this hypothesis, we established the epigenetic and transcriptomic profiles of immune cells from 44 childhood cancer survivors (CCS, > 16 years old) on full remission (> 5 years) who had received chemotherapy alone or in combination with total body irradiation (TBI) and hematopoietic stem cell transplant (HSCT). We found that more than 10 years post-treatment, CCS treated with TBI/HSCT showed an altered DNA methylation signature in T cell, particularly at genes controlling immune and inflammatory processes and oxidative stress. DNA methylation remodeling in T cell was partially associated with chronic expression changes of nearby genes, increased frequency of type 1 cytokine-producing T cell, elevated systemic levels of these cytokines, and over-activation of related signaling pathways. Survivors exposed to TBI/HSCT were further characterized by an Epigenetic-Aging-Signature of T cell consistent with accelerated epigenetic aging. To investigate the potential contribution of irradiation to these changes, we established two cell culture models. We identified that radiation partially recapitulated the immune changes observed in survivors through a bystander effect that could be mediated by circulating factors. CONCLUSION: Cancer treatments, in particular TBI/HSCT, are associated with long-term immune disturbances. We propose that epigenetic remodeling of immune cells following cancer therapy augments inflammatory- and age-related diseases, including metabolic complications, in childhood cancer survivors.

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

Importance: In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. Objective: To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. Design, Setting, and Participants: In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Exposures: Chemotherapy agents known to be toxic to peripheral nerves. Main Outcomes and Measures: The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Results: Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 53 of 100 participants (53.0%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 µV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids. Conclusions and Relevance: Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted long term, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.

'Re-engage' pilot study protocol: a nurse-led eHealth intervention to re-engage, educate and empower childhood cancer survivors.

INTRODUCTION: Many childhood cancer survivors are disengaged from cancer-related follow-up care despite being at high risk of treatment-related late effects. Innovative models of long-term follow-up (LTFU) care to manage ongoing treatment-related complications are needed. 'Re-engage' is a nurse-led eHealth intervention designed to improve survivors' health-related self-efficacy, targeted at survivors disengaged from follow-up. Re-engage aims to overcome survivor- and parent-reported barriers to care and ensure survivors receive the care most appropriate to their risk level. METHODS AND ANALYSIS: This study will recruit 30 Australian childhood cancer survivors who are not receiving any cancer-related care. Participation involves two online/telephone consultations with a survivorship nurse for medical assessment, a case review, risk stratification and creation of a care plan by a multidisciplinary team of specialists. We will assess the feasibility of implementing 'Re-engage' and its acceptability to participants and health professionals involved. The primary outcome will be survivors' health-related self-efficacy, measured at baseline and 1 and 6 months postintervention. Secondary outcomes will include the effect of 'Re-engage' on survivors' health behaviours and beliefs, engagement in healthcare, information needs and emotional well-being. We will also document the cost per patient to deliver 'Re-engage'. If Re-engage is acceptable, feasible and demonstrates early efficacy, it may have the potential to empower survivors in coordinating their complex care, improving survivors' long-term engagement and satisfaction with care. Ideally, it will be implemented into clinical practice to recall survivors lost to follow-up and reduce the ongoing burden of treatment for childhood cancer. ETHICS AND DISSEMINATION: The study protocol has been approved by the South Eastern Sydney Local Health District Human Research Ethics Committee (reference number: 16/366). The results will be disseminated in peer-reviewed journals and at scientific conferences. A lay summary will be published on the Behavioural Sciences Unit website. TRIAL REGISTRATION NUMBER: ACTRN12618000194268.